In a study published in the August 2002 European Journal of Clinical Nutrition, researchers in New Zealand determined that as little as 100 micrograms folic acid added to the diet can lower homocysteine in individuals with elevated levels of this dangerous substance. In a double-blind randomized placebo-controlled trial, seventy men and women with plasma homocysteine greater than or equal to 10 micromoles per liter received 20 grams of breakfast cereal fortified with 100, 200 or 300 micrograms folic acid, or 20 grams unfortified cereal, for four weeks. The participants, whose age range was 29 to 90 years, had their serum folate, plasma homocysteine and other blood values measured at the onset and conclusion of the study. Subjects were asked to keep a four day record of food consumed prior to the study's onset and toward the end of the four week period.

Serum folate levels were found to increase significantly in proportion to the amount of supplemental folic acid consumed. Plasma total homocysteine levels declined by 16% in the group receiving 100 micrograms of folic acid, by 12% in the 200 microgram group and by 17% in the treatment group.

The objective of the study was to determine the minimum effective dose to increase serum folate and significantly reduce plasma homocysteine. The researchers concluded that 100 micrograms was sufficient for this purpose, and noted that when total folic acid intake from all sources is considered, the amounts obtained from fortified foods may be high enough to improve the folate status of young women to reduce neural tube defects in their offspring. However, another study, featured in What's Hot March 12, 2001, demonstrated that levels achieved by fortification, while an improvement, do not lower homocysteine to the maximum level achievable.

July 29, 2002

Does positive thinking about aging lengthen our lives?

A study published in the August 2002 American Psychological Association's Journal of Personality and Social Psychology (http://www.apa.org/journals/psp/description.htm) found that older individuals with positive self-perceptions of aging lived seven and one half years longer than individuals who perceived aging in a less positive light. The Yale University Department of Epidemiology and Public Health researchers analyzed information gathered from 338 male and 322 female participants in the Ohio Longitudinal Study of Aging and Retirement. Participants answered questionnaires twenty-three years earlier which measured their perceptions of aging. For example, subjects were asked whether they agreed or disagreed with the statement, "Things keep getting worse as I get older."

After analyzing mortality rates for the group and adjusting for age, gender, overall health, socioeconomic status and loneliness, the 7.5 year greater lifespan remained for those whose answers on the questionnaires were characteristic of a more positive outlook. The study also found that the will to live accounts partly for the relationship between positive perceptions of aging and lifespan. Cardiovascular response to stress, which can be affected when older individuals are exposed to negative aging stereotypes, may contribute to these findings as well.

Author Becca R Levy PhD, and colleagues write, "The effect of more positive self-perceptions of aging on survival is greater than the physiological measures of low systolic blood pressure and cholesterol, each of which is associated with a longer lifespan of four years or less. The survival advantage of more positive self-perceptions of aging is also greater than the independent contributions of lower body mass index; no history of smoking, and a tendency to exercise, each of these factors has been found to contribute between one and three years of added life . . . Our study carries two messages. The discouraging one is that negative self-perceptions can diminish life expectancy; the encouraging one is that positive self-perceptions can prolong life expectancy. "

July 26, 2002

Men more at risk of death at all ages

The July 27 2002 issue of New Scientist Magazine (http://www.newscientist.com) published a study that examined death rates in twenty countries which found that not only do men not live as long as women on average, but their risk of dying at any age was significantly greater than that of women. In a report presented at the Animal Behavior Society held this month in Bloomington, Indiana, researchers from the University of Michigan in Ann Arbor evaluated statistics from the United States, Russia, Australia, Ireland, El Salvador, Columbia and Singapore among other countries. They found that in the United States the male to female mortality rate increases sharply at adolescence with men younger than fifty years of age twice as likely as women to die, and that this risk was greater for men eighty years of age or older. American men age 20 to 24 had three times the death rate of women, while Columbian men experienced five times this rate.

The researchers also studied ten major causes of death, and found that the increased risk of death for men was consistent for every cause, including accidents, automobile accidents, heart disease and homicides. While deaths from accidents demonstrate the greatest gender discrepancy in external causes, and is seen in young males, the second largest disparity occurs in deaths from diseases in men and women aged sixty and older, with men over one and a half times more likely to die.

Author Randolph Nesse of the University of Michigan Institute for Social Research stated, ""Being male is now the single largest demographic factor for early death. He predicted, "If you could make male mortality rates the same as female rates, you would do more good than curing cancer."

July 24, 2002

Low dose, extended release niacin helps diabetic dyslipidemia.

The altered blood lipid values known as dyslipidemia found in diabetic patients would seem to make these individuals an ideal group to receive the lipid-modifying B-vitamin niacin, yet the concern that niacin raises blood glucose levels has prevented many of these patients from taking advantage of this therapy. However, the July 22 2002 issue of the journal Archives of Internal Medicine published the results of a study showing that sixteen weeks of what is considered to be low dose extended-release niacin improved lipid values of diabetics with minimal changes in glycemic control experienced by participants.

One hundred forty-eight patients with diabetic dyslipidemia were randomized to receive either 1000 or 1500 milligrams of extended release niacin, or a placebo for sixteen weeks. The researchers found that niacin elevated HDL cholesterol and reduced triglyceride levels. The group receiving 1500 mg niacin experienced a 7% reduction in LDL cholesterol. Only four patients discontinued niacin due to inadequate glucose control.

Lead study author and director of the Center for Human Nutrition at the University of Texas Southwestern Medical Center, Dr. Scott Grundy, stated, "Previous reports have shown that niacin in high doses raises blood glucose, but this trial shows that in doses of 1,000 milligrams per day and 1,500 mg/d, niacin therapy was well-tolerated and changes in glycemic control were minimal. Low doses of an extended form of niacin also had favorable effects on blood lipids and lipoproteins . . . Most patients with diabetes will require lipid-lowering therapy. The use of statins to lower LDL cholesterol is becoming routine therapy for the majority of patients; however, this study indicates that the addition of niacin to statin therapy will provide additional benefit for improvement of blood lipids and lipoproteins in patients with diabetes."

The August 2002 issue of the journal, Gut published a study conducted in Ireland which showed that folic acid supplementation can help prevent the increased mucosal cell proliferation in individuals at risk of colon cancer. Twenty patients with recurrent adenomatous polyps of the colon, which have the possibility of becoming cancerous, received two milligrams folic acid per day or a placebo for 12 weeks. Rectal biopsy samples were taken from the participants before supplementation, and at four, twelve and eighteen weeks in order to examine cell proliferation. Blood samples were also taken at these examinations. The patients completed three day dietary questionnaires at the study's onset and following supplementation, and the researchers calculated the amount and type of food consumed.

The researchers found that although mucosal cell proliferation between the groups was similar at the beginning of the study, the group receiving folic acid experienced a reduction in proliferation by the study's conclusion. The most significant reduction took place at the upper aspect of the crypt. Crypts are the indentations in the walls of the colon in which cells grow and replicate, with oldest cells existing at the top. Animal studies have shown that changes in colony mucosal crypt cells are related to changes in tumor risk.

The authors speculate that increasing folic acid may help to protect DNA through its involvement in methylation and its prevention of strand breaks. A deficiency of folate may also impair DNA repair in the mucosa of the colon and lead to chromosomal abnormalities at fragile sites.

The authors conclude that folic acid supplementation can regulate colonic mucosa cell proliferation in patients at risk of colon cancer and note that the effect of the supplements may persist after they are discontinued.

July 17, 2002

Blocking interleukin-1 preserves brain cells

A study published in the July 15 2002 issue of the Journal of Neuroscience revealed that the additional damage that follows an injury to the brain can be halted by inhibiting the protein interleukin-1 (IL-1). Interleukin-1 is a protein that causes inflammation which is released by immune cells in response to injury. Researchers at Penn State College of Medicine examined the effect of brain injury on mice lacking receptors for IL-1. They found that fewer macrophages were attracted to the brain and that the brain's macrophages did not produce substances that would harm healthy cells. Macrophages ingest dead cells and release IL-1 which signals more macrophages to migrate to injured tissue. Study author and associate professor of neuroscience and anatomy at Penn State College of Medicine, Steven Levison, PhD, explained, "The macrophage reaction is a good one in regenerating tissues, but in a nonregenerating tissue like the brain, it can be devastating. These data suggest that cell preservation is achieved by stopping macrophage, or microglial, activation. In addition, the research shows that the initial burst of IL-1 causes more IL-1 to be released, which amplifies the injury response. This causes a runaway inflammation in the brain where you don't want it . . . This study helps us understand why inflammation in the brain is not good and specifically why IL-1 is not good for the brain."

The research team is currently testing the same strain of mice to determine if experimentally induced stroke also results in less damage to the brain in these animals, and plans to study whether they are less susceptible to diseases like multiple sclerosis.

The July 15 2002 issue of the Journal of Neuroscience contained two studies showing that consumption of foods rich in antioxidants may help protect the brain from some of the decline that occurs with aging. The studies were conducted by researchers at the University of South Florida Center for Aging and Brain Repair and James A Haley Veterans Hospital in Tampa, Florida. The first study compared the effects of a diet enhanced with antioxidant-rich spinach to a regular rat chow diet on the rapidity of conditioned response to a stimulus by older rats. Rats who consumed the 2% freeze-dried spinach diet for six weeks were found to have more rapid responses than control animals.

The second study compared the benefits of diets enriched with spirulina, apples or cucumbers in older rats. Spirulina is a rich source of antioxidants, while apples are considered a moderately-rich source, and cucumbers a poor source, although high in fiber. The rats fed diets enhanced with spirulina or apple-enriched diets showed improvement in neuron function, suppressed brain inflammatory substances and lower levels of the oxidative damage marker malondialdehyde after two weeks. The rats who received spirulina also showed a reversal in the adrenergic neural function impairment that occurs with age. Rats on the cucumber-supplemented diet did not show any benefits.

Lead author and professor at the University of South Florida Center for Aging and Brain Repair, Paula Bickford PhD, noted that studies suggest the lifelong accumulation of free radicals can slow mental processes as we age. She commented, "If these preclinical findings translate to humans, it suggests that eating a diet high in antioxidant-rich fruits and vegetables may help reverse declines in learning and memory as you get older."

A statement by the Joint Stroke Guideline Development Committee of the American Academy of Neurology and the American Stroke Association, published in the July 2002 issue of the journal Stroke, is recommending that 160 to 325 mg aspirin be given to ischemic stroke patients within forty-eight hours of the event to diminish the risk of death and disability. The statement is the outcome of a review of ten studies on the subjects of antiplatelet therapies such as aspirin and anticoagulants such as heparin, and their effect on ischemic stroke. Ischemic stroke occurs when there is blockage by a blood clot of an artery that supplies blood to the brain.

The researchers found a small but significant decline in mortality and disability from stroke when aspirin was provided to patients within forty-eight hours, but that anticoagulants did not have the same effect. Lead author and professor and head of the department of neurology and professor of medicine, University of Arizona, Arizona Health Science Center, Bruce Coull, MD, explained, "There is some evidence that a fixed dose of heparin given subcutaneously might be helpful for preventing recurrent stroke, but the benefit is balanced against the complication of increased hemorrhage. With the net effect, there is no benefit to that treatment. Therefore, we are not recommending that one use a fixed dose of heparin given subcutaneously to prevent stroke recurrence."

The authors did, however, recommend subcutaneous heparin for deep-vein thrombosis prevention in patients who are at risk.

Dr Coull summarized, "These results emphasize the importance of reviewing all the evidence to develop practice guidelines. Despite decades of use and physiologic reasons for its use, there were surprisingly few randomized trials that addressed the effects of using heparin and other anticoagulants within a few hours of onset of symptoms."

July 10, 2002

Breast cancer increase halts HRT trial

A major clinical trial seeking to determine the risks and benefits of estrogen and progestin hormone replacement in menopausal women was stopped due to the increased risk of invasive breast cancer experienced by trial participants. The Women's Health Initiative (WHI) study, sponsored by the National Institute of Health's National Heart, Lung, and Blood Institute, was scheduled to end in 2005, but was halted after an average follow-up period of 5.2 years. Although participants in the study experienced a lower incidence of colon cancer and fewer fractures, in addition to a 26% increase in breast cancer, the study also revealed a 41% increase in stroke risk, a 29% increase in heart attacks, twice the rate of blood clots and a 22% increase in cardiovascular disease compared to women who received a placebo.

National Heart, Lung and Blood Institute Director Claude Lenfant, MD, commented, "We have long sought the answer to the question: Does postmenopausal hormone therapy prevent heart disease and, if it does, what are the risks? The bottom-line answer from WHI is that this combined form of hormone therapy is unlikely to benefit the heart. The cardiovascular and cancer risks of estrogen plus progestin outweigh any benefits -- and a 26 percent increase in breast cancer risk is too high a price to pay, even if there were a heart benefit. Similarly, the risks outweigh the benefits of fewer hip fractures. Menopausal women who might have been candidates for estrogen plus progestin should now focus on well-proven treatments to reduce the risk of cardiovascular disease, including measures to prevent and control high blood pressure, high blood cholesterol, and obesity. This effort could not be more important: heart disease remains the number one killer of American women."

The report will be published in The Journal of the American Medical Association.

July 1, 2002

Soy and herbal supplement shows success in mice and humans with lung cancer

A pilot study published in the journal Nutrition and Cancer, volume 39 number 1, 2001, demonstrated the success of a dietary supplement, referred to as "selected vegetables", in prolonging survival in patients with stages IIIB and IV non-small cell lung cancer, which has a poor response to systemic treatments. The median survival of stage IV patients is 8 to 15 months with recently introduced chemotherapy protocols, and 3 to 5 months with supportive care only. The study also evaluated the anticancer activity of the supplement in mice with lung tumors.

The selected vegetable supplement used in the study was developed by lead researcher Alexander Sun, MD of the Connecticut Institute for Aging and Cancer at Milford, Connecticut, and contains soy, mushrooms, mung beans, dates, scallion, garlic, lentils, leek, hawthorn fruit, onion, ginseng, angelica root, licorice, dandelion root, senegal root, ginger, olive, sesame seeds and parsley. An evaluation of the supplement revealed the presence of inositol hexaphosphate (IP6), daizein and genistein from soy, and coumestrol. Mice given a diet consisting of 5% of the supplement from one week prior to tumor inoculation experienced a 53-74% inhibition of tumor growth rate compared to controls. Of the fourteen human non-small cell lung carcinoma patients who were administered the supplement daily for two to forty-six months along with conventional therapy, one experienced a complete regression of brain lesions following radiotherapy combined with use of the supplement, and another patient was tumor free for over eleven years.

The remaining patients experienced a median survival time of 33.5 months. There were no signs of toxicity in any of the patients. The improvements shown in this study warrant a large clinical trial of the selected vegetable supplement as an adjuvant therapy to radiation and surgery in patients with non-small cell lung cancer.

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